Ophthalmic examinations were conducted with accumulation of historical control data in Crl:CD(SD) rats from 2004 to 2007 and the spontaneous ocular abnormalities were analyzed. A total of 484 control rats from 22 toxicological studies were examined with slit lamp biomicroscopy and indirect ophthalmoscopy. The age of animals at examination ranged from 8 to 31 weeks and the number of control animals per study was 10 to 20 per sex.
There was a high incidence of ocular abnormalities in the cornea and lens with incidences of 47% and 31%, respectively. These abnormalities consisted of opacities. The corneal finding observed mostly was interpalpebral punctate opacity. The lens opacities were observed in the anterior subcapsular, anterior cortical, cortical nuclear junction, nuclear, posterior cortical and posterior capsular. Of the lens opacities, nuclear changes were observed with the highest incidence of 23% and the anterior cortical opacities were observed with the second highest incidence of 8%. The incidence of ocular abnormalities in the conjunctiva, iris, vitreous, retina and choroid were 2% and below. The incidence of corneal and lens opacities were very variable depending on the lot of rats and were not very related to age range examined.

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Three percent N-acetylcysteine ophthalmic solution (PAPITEIN®, Senju pharmaceutical Co., Ltd., Osaka) is widely known to be useful for the treatment of canine and feline corneal lesions in traumatic keratitis and corneal ulcer by its anti-collagenase effect. On the other hand, it is also known that repeated instillations of a highly concentrated N-acetylcysteine solution remove the ocular surface mucin in rabbits. Therefore, we investigated whether 3% N-acetylcysteine ophthalmic solution led to damage on the ocular surface by repeated instillations of it into the left eye and of saline into the right eye of beagle dogs at intervals of 2 hours, 6 times a day for 2 weeks. During instillation period, anterior ocular findings were evaluated by vital staining with fluorescein on cornea and with lissamine green on cornea and conjunctiva, and histopathological findings of isolated cornea were also evaluated after 2 week repeated instillations of them. No adverse effects on the ocular surface were observed by both vital staining and histopathological findings with a microscope and a scanning electron microscope. These findings suggest that 3% N-acetylcysteine ophthalmic solution does not reduce mucin covered on the ocular surface and does not induce the damage of corneal epithelium in dogs when the solution is repeatedly instilled 6 times a day for 2 weeks.

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Retinal toxicity is one of the serious toxicities because of the potential risk of blindness, and electroretinography is a useful method for assessing the retinal toxicity of compounds. Outbred ICR mice are commonly used for the preclinical safety evaluation of compounds. Although it is important for preclinical safety evaluation to understand the characteristics of experimental animals, there have been no reports about the characterization and incidence of spontaneous retinal dysfunction in ICR mice. In this study, electroretinogram (ERG) recordings were performed on Crlj: CD1(ICR) mice (total 154 mice) to determine the characterization and incidence of spontaneous retinal dysfunction.
After more than 12 h-dark adaptation, scotopic ERGs were recorded under anesthesia, followed by 10-min light adaptation and then photopic ERG recordings. Ophthalmological examination, mating experiment and histopathological examination of the eyes were also performed on mice which showed retinal dysfunction.
ERG recordings revealed that the incidences of cone dysfunction and rod-cone dysfunction were 8.4% and 0.6%, respectively. There were no abnormalities relating to retinal dysfunction in the fundus or retinal structures in the mice showing such retinal dysfunction. When one female mouse with each type of retinal dysfunction was mated with male ICR-derived retinal dysfunction (IRD)1 mouse which was a mouse model for rod-cone dysfunction derived from the ICR colony, the F₁ mice showed the same types of retinal dysfunction as their dams, indicating that these were inheritable.
In conclusion, it was demonstrated that Crlj:CD1(ICR) mice included animals showing spontaneous retinal dysfunction without abnormal retinal structures and when ICR mice are used for evaluation of the potential of a compound to induce retinal toxicity it will be valuable to perform selection by doing ERG recordings before treatment.

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In the toxicity studies detection of ocular toxicity, ophthalmological examinations are carried out to select suitable animals for the studies during the quarantine period. During this period, spontaneous abnormalities are observed. In this report, we focus on fundus hemorrhage of these abnormalities in Fischer 344 (F344) and Sprague-Dawley (SD) rats and report them with prognosis.
On ophthalmological examinations in F344 rats at 5 weeks of age, spotty hemorrhage in fundus was observed in 5 of 249 males and 1 of 249 females, and flame-shaped hemorrhage in fundus was observed in 1 of 249 males. Of the spotty hemorrhage, 4 males showed band-shaped hyperreflective fundus with fundus hemorrhage. One female and 2 males with spotty hemorrhage at 5 weeks of age had diffused hyperreflective fundus at 9 or 13 weeks of age. Another male with the flame-shaped hemorrhage at 5 weeks of age had dark-red foci on hemorrhage area at 10 weeks of age but abnormalities including dark-red foci were not observed at 12 weeks of age. On ophthalmological examinations in SD rats at 4 weeks of age, spotty hemorrhage with band-shaped hyperreflective fundus was observed in 1 of 441 females. On the other hand, 1 in 441 male had a ring hemorrhage centering on the retinal artery at 4 weeks of age, and this ring hemorrhage was not found and hyperreflective fundus was observed on the same area at 16 weeks of age. In histopathological examination for diffused hyperreflective fundus at 11 or 13 weeks of age in 2 F344 rats, the inner nuclear, inner plexiform and ganglionic cell layers was thin or not present.
Based on these findings, it was suggested that there were relationships between spotty hemorrhage and hyperrefl ective fundus. In the cases of diffuse hyperrefl ective fundus, atrophic change of inner nuclear layer to ganglion cell layer were indicated histopathologically.

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A 7-year-old female Chihuahua presented with a complaint of localized central corneal opacity and distorted iris in the right eye. Ophthalmic evaluation with a slit-lamp biomicroscope revealed several persistent pupillary tissue strands arising from a minor iridal circle and iris collarette attached to the corneal endothelium, causing corneal opacity. The mobility of the iris was impaired, and the pupil was distorted and partly obscured by the strands. Other ophthalmic findings included multiple and small brown-pigmented uveal cysts at the pupillary margin and slightly localized iris hyperemia around the distorted iris. Uveal cysts can be congenital and acquired, but their cause is largely unknown. In this case, the possible cause of the uveal cyst formation and/or enlargement was suggested to be the repeated expansion and contraction due to the physical obstruction of the iris by the pupillary strands.

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